Ligand-gated ion channel
Ligand-gated ion channels (LGICs), also referred to as ionotropic receptors or channel-linked receptors, are a group of transmembrane ion channels that are opened or closed in response to the binding of a chemical messenger (i.e., a ligand), such as a neurotransmitter. The binding site of endogenous ligands on LGICs protein complexes are normally located on a different portion of the protein (an allosteric binding site) compared to where the ion conduction pore is located. The direct link between ligand binding and opening or closing of the ion channel, which is characteristic of ligand-gated ion channels, is contrasted with the indirect function of metabotropic receptors, which use second messengers. Ligand-gated ion channels are also different from voltage-gated ion channels (which open and close depending on membrane potential), and stretch-activated ion channels (which open and close depending on mechanical deformation of the cell membrane). Regulation The ion channel is regulated by a ligand and is usually very selective to one or more ions like Na+, K+, Ca2+, or Cl-. Such receptors located at synapses convert the chemical signal of presynaptically released neurotransmitter directly and very quickly into a postsynaptic electrical signal. Many LGICs are additionally modulated by allosteric ligands, by channel blockers, ions, or the membrane potential. Structure Each subunit of the pentameric channels consist of the extracellular ligand-binding domain and a transmembrane domain. Each transmembrane domain in the pentamer includes four transmembrane helixes. Example: nicotinic acetylcholine receptor The prototypic ligand-gated ion channel is the nicotinic acetylcholine receptor. It consists of a pentamer of protein subunits, with two binding sites for acetylcholine, which, when bound, alter the receptor's configuration and cause an internal pore to open. This pore allows Na+ ions to flow down their electrochemical gradient into the cell. With a sufficient number of channels opening at once, the intracellular Na+ concentration rises to the point at which the positive charge within the cell is enough to depolarize the membrane, and an action potential is initiated. Classification Many important ion channels are ligand-gated, and they show a significant degree of homology at the genetic level. LGICs are classified into three superfamilies: Cys-loop receptors The cys-loop receptors contain a characteristic loop formed by a disulfide bond between two cysteine residues and are subdivided into the type of ion that the corresponding channel conducts (anionic or cationic) and further into families defined by the endogenous ligand. They are usually pentameric. Anionic Cationic Ionotropic glutamate receptors The glutamate receptors bind the neurotransmitter glutamate. They form tetramers. ATP-gated channels ATP-gated channels open in response to binding the nucleotide ATP. They form trimers. Clinical relevance Ligand-gated ion channels are likely to be the major site at which anaesthetic agents and ethanol have their effects, although unequivocal evidence of this is yet to be established. In particular, the GABA and NMDA receptors are affected by anaesthetic agents at concentrations similar to those used in clinical anaesthesia. See also *Chronotropic *Receptor (biochemistry) *Glycine receptor *P2X Receptor *Sodium ion channel References External links * * Ligand-Gated Ion Channel database at European Bioinformatics Institute. Verified availability April 11, 2007. Further reading * Category:Electrophysiology Category:Ion channels Category:Ionotropic receptors Category:Molecular neuroscience Category:Neurochemistry Category:Protein families